Neuroscience and Biobehavioral Reviews 107 (2019) 399–421

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Neuroscience and Biobehavioral Reviews

journal homepage: www.elsevier.com/locate/neubiorev

The effect of high fat, high sugar, and combined high fat-high sugar diets on T
spatial learning and memory in rodents: A meta-analysis
Kirsten N. Abbotta, Christopher K. Arnottb, R. Frederick Westbrooka, Dominic M.D. Tranb,
⁎

a
School of Psychology, The University of New South Wales, Australia
b
School of Psychology, The University of Sydney, Australia

ARTICLE INFO ABSTRACT

Keywords: Evidence from human and animal studies suggests that high-energy diets impair cognitive function. However,
Rodent models the conditions for such impairments are unclear as studies have differed in the type and duration of diet exposure
High energy diet as well as in the tasks used to assess deficits in cognition. Here, we focused on hippocampal-dependent tasks. We
High fat diet conducted separate meta-analyses of the results from rodent studies using: 1) different diets (high in fat, high in
High sugar diet
sugar, or high in both fat and sugar); and 2) different tasks to assess hippocampal-dependent spatial learning and
Hippocampus
Spatial learning and memory
memory (water maze, place recognition, radial arm maze, and spontaneous alternation). We focused on the
effects of relatively short-term dietary manipulations and, therefore, restricted our analyses to studies that
provided the diet for 2 months or less. The meta-analyses showed that each type of diet and task adversely
affected performance, with the largest effect produced by exposure to a combined high fat-high sugar diet and
the use of the radial arm maze to assess the effect of such diets on cognition.

1. Introduction
The modern diet contains many foods and drinks that are rich in
saturated fat and sugar (Kearney, 2010; Khatibzadeh et al., 2016;
Ritchie and Roser, 2017; Vasileska and Rechkoska, 2012; reviewed in
Cordain et al., 2005; Popkin et al., 2012). It has long been recognized
that excessive intake of this diet is associated with increased body
weight, even obesity, some forms of cancer, as well as metabolic and
cardiovascular diseases (Carrera-Bastos et al., 2011; Cordain et al.,
2005; Mente et al., 2009). More recent epidemiological evidence has
indicated that this diet is also associated with deficits in cognition
(reviewed in Kanoski and Davidson, 2011, and Yeomans, 2017). For
example, longitudinal studies of middle-aged (Eskelinen et al., 2008)
and older adults (Gustaw-Rothenberg, 2009; Morris et al., 2004;
Okereke et al., 2012; Naqvi et al., 2011; Roberts et al., 2012) showed
that consumption of diets high in saturated fat and refined carbohy-
drates was negatively correlated with overall cognitive “well-being”
(e.g., memory, executive function, psychomotor speed) in later life and
positively correlated with neurological disorders such as Alzheimer’s
disease (reviewed in Pugazhenthi et al., 2017).
Hippocampal-dependent forms of cognition seem to be particularly
susceptible to the detrimental effects of diets that are high in saturated
fat and/or refined sugar. A cross-sectional study of young adults
(Francis and Stevenson, 2011) found that self-reported intake of so-
called “fast” foods predicted scores on subtests of the Wechsler Memory
Scale Revised (WMS-R; Wechsler and Stone, 1987) that are sensitive to
left hippocampal damage, specifically, the verbal paired associates and
logical memory subtests. However, intake of such foods failed to predict
scores on the hippocampal-independent, digit span subtest of the WMS-
R. Similarly, cross-sectional research in healthy young women found
that habitual intake of saturated fat predicted lower scores on the
CANTAB eclipse (v3) suite of cognitive tests (Cambridge Cognition Ltd.,
2006) that are sensitive to hippocampal damage, such as verbal re-
cognition memory, delayed-matching-to sample, and paired associate
learning (Gibson et al., 2013). Finally, there is even evidence that
cognitive deficits can be detected after relative short exposures to such
diets. Attuquayefio et al. (2017) found a statistically significant pre- to
post decline in scores on the Hopkins Verbal Learning Task Revised in
healthy adults who consumed a breakfast high in saturated fat and
refined sugar for four days, but not in a control group of adults that
consumed a low fat, low sugar diet of similar palatability.
Rodent models have confirmed that diets high in saturated fat,
sugar, or both fat and sugar are associated with deficits in tasks that
require the hippocampus and surrounding cortices (see Table 1). Sev-
eral studies have reported such dietary effects in the use of spatial cues
to navigate to the hidden platform in the Morris (e.g., Che et al., 2018)
and radial arm water mazes (e.g., Alzoubi et al., 2013a, b; Alzoubi
et al., 2018), or to avoid arms that have been visited and depleted of

⁎
Corresponding author.
E-mail address: minh.d.tran@sydney.edu.au (D.M.D. Tran).

https://doi.org/10.1016/j.neubiorev.2019.08.010
Received 11 February 2019; Received in revised form 2 August 2019; Accepted 12 August 2019
Available online 24 August 2019
0149-7634/ © 2019 Elsevier Ltd. All rights reserved.
 Table 1
Body weight and metabolic parameters of experimental and control animals provided a high fat, high sugar, or high fat-high sugar diet (* = unless otherwise stated; HFD = high fat diet; HSD = high sugar diet;
HFHS = high fat high sugar diet; CD = control diet; MWM = Morris Water Maze; PR = Place recognition; RAM = Radial arm maze; RAWM = Radial Arm Water Maze; SA = Spontaneous Alternation; RI = Retention
Interval; GTT = Glucose Tolerance Test; ITT = Insulin Tolerance Test; TC = Total Cholesterol; HDL = High Density Lipoprotein; LDL = low Density Lipoprotein; ELISA = Enzyme Linked Immunosorbent Assay; HOMA
K.N. Abbott, et al.

= Homeostatic Model Assessment; QUICKI = Quantitative Insulin Sensitivity Check).

Study Species & Experimental Diet Spatial Task Diet-induced Body Weight (BW) Blood* Glucose Level Plasma* Insulin Level HOMA Index Plasma* Others
Strain [Sex & Classification for Meta- Deficit (BGL) Triglycerides
Age] Analysis

Abbott et al (2016) Expt Sprague HSD PR Yes No effect – – – – –

1 Dawley rats Object-in- No (Female);
[Male & Place Yes (Male)
Female]
Alzoubi et al (2013a) Wistar rats HFD (labelled Western Diet RAWM (6- Yes Sig effect – – – – –
Expt 1 [Male] by authors) arm) (P < .05)
Alzoubi et al (2013b) Wistar rats HFD (labelled High Fat RAWM (6- Yes Sig effect – – – – –
Expt 1 [Male] Cholesterol Diet by authors) arm) (P < .05)
Alzoubi et al (2018) Wistar rats HFD RAWM (6- Yes – – – – – –
[Male] arm)
Arnold et al (2014) C57BL/6 J Extreme HFD T-Maze SA Yes Sig effect Sig effect (P < .001) – – – –
mice [Male] (P < .01)
Moderate HFD T-Maze SA Yes Sig effect Sig effect on BGL and – – – –
(P < .05) GTT response
(Ps < .05)
Ayabe et al (2018) C57BL/6 J HFD PR No Sig effect [week – – – Sig effect –
mice [Male] 3+] (Ps < .01) (P < .01)
Beilharz et al (2014) Sprague HFHS (labelled Cafeteria PR Yes (all tests) Sig effect [day – – – – –
Expt 1 Dawley rats Diet with Sucrose solution by 16+] (P < .05)
[Male] authors)

400
Beilharz et al (2014) Sprague HSD PR Yes (all tests) No effect – [ELISA] no effect – No effect [ELISA] no effect on
Expt 2 Dawley rats plasma leptin
[Male] HFHS (labelled Cafeteria Yes (all tests) Sig effect [day – [ELISA] sig effect Sig effect [ELISA] sig effect
Diet with Sucrose solution by 15+] (Ps < .05); (P < .05) (P < .05) plasma leptin
authors) (P < .05)
HFHS (labelled Cafeteria Yes (all tests) Sig effect [day – [ELISA] no effect Sig effect [ELISA] sig effect
Diet by authors) 15+] (Ps < .05); (P < .05) plasma leptin
(P < .05)
Beilharz et al (2018) Sprague HFHS (labelled Cafeteria PR Yes (all tests) Sig effect No effect – – – –
Dawley rats Diet with Sucrose solution by (P < .001)
[Male] authors)
Boitard et al (2014) Wistar rats HFD MWM No Sig effect Sig effect (P < .05) No effect – No effect No effect on plasma
[Male] (P < .05) cholesterol; sig effect
plasma leptin
(P < .05)
Che et al (2018) SAMP8 mice HFD MWM Yes – – – – – –
[Male]
Denver et al (2018) C57BL/6 J HFD 10 days MWM No Sig effect [day 4+] – – – – –
mice [Male] (Ps < .05)
HFD 26 days No Sig effect [day – – – – –
24+] (P < .05)
HFD 8 weeks No Sig effect [week – – – – –
2+] (Ps < .05)
Gergerlioglu et al (2016) Wistar rats HFD MWM Yes No effect No effect – – – –
Expt 1 [Male] HSD No No effect No effect – – – –
Hargrave et al. (2016) Sprague Ketogenic Diet Y-maze SA No No effect No effect No effect – – –
Expt 1 Dawley rats HFHS(labelled high-fat, Y-maze SA Yes (10 day No effect No effect No effect – – –
[Male] high-dextrose “Western” diet test); No (40
by authors) day test)
Neuroscience and Biobehavioral Reviews 107 (2019) 399–421

(continued on next page)

 Table 1 (continued)

Study Species & Experimental Diet Spatial Task Diet-induced Body Weight (BW) Blood* Glucose Level Plasma* Insulin Level HOMA Index Plasma* Others
Strain [Sex & Classification for Meta- Deficit (BGL) Triglycerides
Age] Analysis
K.N. Abbott, et al.

Jamshed et al (2014) Sprague HFD (labelled cholesterol- MWM Yes – – – – Sig effect week 6 Sig effect on TC, LDL,
Expt 1 Dawley rats chocolate-butter fat diet by (P < .01) & HDL:LDL ratio in
[Male & authors) week 6 (Ps < .01)
Female]
Jurdak et al (2008) Long– Evans HFD MWM No Sig effect Overnight Fasted. No – – No effect No effect on TC, HDL,
rats [Male] (P < .05) effect BGL or GTT or non-HDL.
response
HSD No (24-hr RI); Sig effect Overnight Fasted. Sig – – Sig effect No effect on TC, HDL,
Yes (10-day RI) (P < .05) effect BGL (P < . 01) (P < .05) or non-HDL.
but not GTT response
Kanoski and Davidson Sprague HFHS (labelled High Energy RAM Yes Sig effect [day – – – – –
(2010) Dawley rats Diet by authors) (8 ar m) 14+] (Ps < .05)
[Male]
Kendig et al (2013) Hooded Wistar HSD MWM Yes (Probe No effect 6 -hour Fasted. Sig – – – –
rats [Male & tests 1-3); No effect [day 29+]
Female] (28-day RI) (main effect,
P < .05) but not day
14
Liang et al (2015) Sprague HFD MWM Yes – – – – – –
Dawley rats
[Male]
Magnusson et al (2015) C57BL/6 J HFD MWM No Sig effect [week – – – – –
mice [Male] MWM Yes 4+] (Ps < .05).
Reversal

401
Task
PR No
HSD MWM No No effect – – – – –
MWM Yes
Reversal
Task
PR No
Mirzaei et al (2018) Wistar rats HFD MWM Yes – – – – – –
[Male]
Molteni et al (2004) Fisher 344 rats Powdered HFHS MWM Yes – – – – – –
[Female]
Moreira et al (2014) Swiss Albino HFD (labelled PR Yes No effect No effect on plasma – Sig effect Sig effect on TC, non-
Mice [Male] Hypercholestermic Diet by glucose (P < .05) HDL, & HDL
authors) (Ps < .05)
Park et al (2018) ICR mice HFD Y-Maze SA Yes Sig effect [week – – – – –
[Male] 5+] (Ps < .05)
Pathan et al (2008) Sprague HFD MWM Yes Sig effect [ELISA] sig effect [ELISA] sig effect – [ELISA] sig effect [ELISA] sig effect on
Dawley rats (P < .05) (P < .001) (P < .001) on blood trigs blood TC (P < .001)
[Male] (P < .001)
Pratchayasakul et al Wistar rats HFD MWM No No effect 12 -hour Fasted. No 12 -hour Fasted. No effect 12 -hour Fasted. 12 -hour Fasted. No
(2015) [Female] 4 effect on plasma [ELISA] no effect No effect effect on TC, LDL, or
weeks old glucose or GTT HDL.
response
Wistar rats No Sig effect 12 -hour Fasted. No 12 -hour Fasted. Sig effect 12 -hour Fasted. 12 -hour Fasted. Sig
[Female] 8 (P < .05) effect on plasma [ELISA] sig effect (P < .05) No effect effect on TC, & LDL
weeks old glucose or GTT (P < .05) (Ps < .01) but not
response HDL
(continued on next page)
Neuroscience and Biobehavioral Reviews 107 (2019) 399–421
 Table 1 (continued)

Study Species & Experimental Diet Spatial Task Diet-induced Body Weight (BW) Blood* Glucose Level Plasma* Insulin Level HOMA Index Plasma* Others
Strain [Sex & Classification for Meta- Deficit (BGL) Triglycerides
Age] Analysis
K.N. Abbott, et al.

Ross et al (2013) Sprague HFHS PR No Sig effect – – – – –

Dawley rats (P < .05)
[Male]
Scichilone et al (2016) Sprague Ketogenic Diet MWM No No effect Sig effect week 2 – – – –
Dawley rats (P < .01), but not
[Male] week 4 or 8
Silva et al (2005) Wistar rats Ketogenic Diet MWM No – – – – – –
[Male]
Spencer et al (2017) F344xbn F1 HFD MWM No Sig effect No effect [ELISA] no effect – – –
rats [Male] 3- (P < .05)
months old
F344xbn F1 No Sig effect No effect [ELISA] no effect – – –
rats [Male] 24- (P < .05)
months old
Spinelli et al (2017) C57BL/6 J HFD MWM Yes – – [ELISA] sig effect – – –
mice [Male] (P < .05)
Takechi et al (2017) C57BL6/J mice High Fat Fructose Diet MWM No Sig effect Sig effect on blood [ELISA] sig effect Non-fasted. – –
[Male] (P < .001) glucose and hba1c (P < .05) Sig effect
(P < .01) (P < .01)
Thirumangalakudi et al C57BL/6 mice HFD RAWM Yes – – – – – –
(2008) (8 ar m)
Tran and Westbrook Sprague HFHS PR Yes (all tests) Sig effect overall – – – – –
(2015) Expt 1 Dawley rats (P < .001) but not
[Male] at first test (day 6-

402
7)
Tran and Westbrook Sprague HFHS PR Yes – – – – – –
(2018) Expt 1 Dawley rats
[Male]
Valladolid-Acebes et al C57BL/6 J HFD RAM Yes Sig effect [week 6 -hour Fasted. No 6 -hour Fasted sig – 6-hour Fasted. No 6 -hour Fasted. No
(2011) mice [Male] (8 ar m) 2+] (Ps < .001) effect effect (P < .001) effect effect on plasma
leptin
Valladolid-Acebes et al C57BL/6 J HFD PR Yes Sig effect No effect No effect – – Sig effect plasma
(2013) Expt 1 mice [Male] (P < .001) leptin (P < .001)
Valladolid-Acebes et al PR No Sig effect Sig effect (P < .05) No effect – – Sig effect plasma
(2013) Expt 3 (P < .001) leptin (P < .001)
Wei et al (2018) C57BL/6 J HFD MWM Yes Sig effect [week – – – – –
mice [Male] 2+] Ps < .05)
Woodie and Blythe Sprague HFD MWM No Sig effect (BW and 4 - 6 hour Fasted. No 4 - 6 hour Fasted. – 4 - 6 hour Fasted. 4-6 hour Fasted. No
(2018) Dawley rats MWM No % BW change; effect [ELISA] no effect vs No effect effect on QUICKI
[Male] Reversal Ps < .05); CD; sig effect vs
Task HfruD (P < .05).
High Fructose Diet MWM No No effect (BW and 4 - 6 hour Fasted. No 4 - 6 hour Fasted. – 4 - 6 hour Fasted. 4-6 hour Fasted. No
MWM No % BW change) effect. [ELISA] no effect vs No effect effect on QUICKI
Reversal CD
Task
Wu et al (2003) Expt 1 Sprague Powdered HFHS MWM No – – – – – –
Dawley rats
[Male]
Xu and Reichelt (2018) Sprague HSD PR Yes No effect – – – – –
Dawley rats
[Male]
Xu et al (2018) C57BL/6 J HFD MWM Yes Sig effect [week Sig effect on BGL and 4 -hour Fasted. Sig – Sig effect on serum Sig effect of serum
mice [Male] 2+] (Ps < .05) GTT response effect on ITT response trigs (P < .05) TC, LDL, & HDL
(Ps < .01) (Ps < .01) (Ps < .01)
Neuroscience and Biobehavioral Reviews 107 (2019) 399–421
K.N. Abbott, et al.
food in the radial arm maze (e.g. Kanoski and Davidson, 2010). Other
studies have found deficits in short-term place, but not object re-
cognition memory (e.g., Abbott et al., 2016; Beilharz et al., 2014; Tran
and Westbrook, 2015), and in spontaneous alternation tasks in Y-
(Hargrave et al., 2016; Park et al., 2018) and T-mazes (Arnold et al.,
2014). Deficits in these tasks have been observed in rodents fed such
diets across time periods that have ranged from months (e.g., Molteni
et al., 2002) to weeks (Abbott et al., 2016; Hargrave et al., 2016), and
even days (Beilharz et al., 2014; Kanoski and Davidson, 2010; Murray
et al., 2009; Tran and Westbrook, 2015), indicating that deficits can
occur rapidly, well in advance of diet-induced increases in body weight.
Although diet-induced deficits in cognition are relatively well-
documented, there have also been failures to detect such effects. For
example, rats fed a high fat-high sugar diet for four weeks (Ross et al.,
2013) or mice fed a high fat diet for seven weeks (Ayabe et al., 2018)
did not differ significantly from chow-fed controls in the place re-
cognition memory task at four hour (or longer) retention intervals.
Further, several investigators (Jurdak et al., 2008; Pratchayasakul et al.,
2015; Scichilone et al., 2016; Silva et al., 2005; Zhao et al., 2004) failed
to detect differences in spatial memory in the Morris water maze be-
tween rats fed a high fat diet for four to eight weeks and chow-fed
control. Finally, older (eight week old) mice placed on a high fat diet for
eight weeks failed to show a deficit in place recognition memory at a
one hour retention interval, whereas younger (five week old) placed on
that diet for that length of time did show a deficit in place recognition
memory (Valladolid-Acebes et al., 2013).
A major difficulty in interpreting the discrepant findings is due to
the procedural variation across studies, especially in the dietary ma-
nipulations and the behavioral tasks used to assess the effects of these
manipulations. One of the most notable differences between studies is
diet composition. For example, lard is typically used to increase the
amount of fat in the diet (Che et al., 2018; Kang et al., 2014; Wei et al.,
2018), but saturated fatty acids (Moreira et al., 2014; Murray et al.,
2009; Spinelli et al., 2017), hydrogenated vegetable oil (Jurdak et al.,
2008), and suet (Gergerlioglu et al., 2016) have also been used. The
total content of fat has also varied between studies, ranging from 18 g/
kg (Che et al., 2018) to approximately 47.5 g/kg of lard (Scichilone
et al., 2016; Zhao et al., 2004). Sugar content also varies across studies,
ranging from sucrose solution concentrations of 10% (Abbott et al.,
2016; Kendig et al., 2013) to 32% (Jurdak et al., 2008). Finally, other
studies have altered the sugar content of the solid foods in the diet
(Gergerlioglu et al., 2016; Magnusson et al., 2015). A second notable
difference is the task used to assess cognitive ability. These tasks in-
clude the various types of mazes and recognition memory paradigms.
Moreover, there are between-study differences in the parameters used
in each of these tasks. For example, studies using the Morris water maze
differed in the number of acquisition trials, the duration of the interval
between trials as well as that between the final acquisition trial and the
first test trial (where the hidden platform is absent or moved to a new
location).
The several failures to replicate reports of diet-induced deficits in
hippocampal-dependent forms of learning and memory raise the pos-
sibility that such deficits are relative fragile. Alternatively, such deficits
may be more readily induced by certain dietary manipulations and/or
the tasks and protocols used to assess their effects. While this topic has
been extensively reviewed (see Beilharz et al., 2015; Cordner and
Tamashiro, 2015; Kanoski and Davidson, 2011; Yeomans, 2017), as far
as we are aware, an analysis of the circumstances which do or do not
produce diet-induced deficits in cognition has not been conducted. We
aimed to provide such an analysis by subjecting some of the published
literature on diet-induced deficits in cognition to a meta-analysis. More
specifically, we sought, first, to assess the contribution of diets high in
saturated fat, refined sugar, or both, to impairments of spatial learning
and memory, and, second, to examine whether inconsistent findings in
the literature were due to differences in the composition of the diet
and/or the behavioral task used to assess its effects. We used two
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Neuroscience and Biobehavioral Reviews 107 (2019) 399–421
criteria for inclusion in analysis. First, we only included studies in
which rodents were provided with the diet for a maximum of eight
weeks (or two months). We did so on the assumption that such rela-
tively short dietary manipulations would be more likely to allow us to
detect any differential effects of the diet composition and/or behavioral
task used for assessment of hippocampal-dependent learning and
memory. Inspection of the literature indicated that eight weeks of
dietary exposure was both short enough to reveal differences and long
enough to provide a sufficient sample for analysis. We note that some
studies included in the meta-analysis report disturbances in metabolic
parameters, such as hyperglycemia, insulin resistance, and body weight
gain (see Table 1 and Discussion), but did not incorporate these dis-
turbances into the analyses due to the lack of statistical power arising
from the large variability in the parameters measured and reported
across studies. The second inclusion criterion was studies that used
rodents older than four weeks. We did so in order to ensure that the
animals were weaned, which typically occurs between postnatal day 21
to 28 (Sengupta, 2011, 2013), and to avoid any interaction effects of
dietary interventions on developmental processes, such as hippocampal
maturation, which occurs at approximately postnatal day 21 (Fan et al.,
2018; Radic et al., 2017; Semple et al., 2013).
2. Method
2.1. Eligibility criteria
The meta-analysis was limited to published, peer-reviewed research
that fed rats or mice diets high in either fat or sugar, or high in both fat
and sugar. To be included in the analysis, the animals were required to
be at least 4 weeks of age at the start of diet administration and be on
the diet for no longer than 8 weeks (or 2 months). For studies that used
transgenic rodent models, the only data included for analysis were from
control and diet intervention wild type animals. For studies that in-
cluded a drug manipulation, the only data included for analysis was
taken from control and diet intervention animals that received saline
administration. Studies that used a maternal diet manipulation were
excluded. All the included studies used a hippocampal-dependent task,
specifically, the Morris water maze (Compton et al., 1997), radial arm
maze and radial arm water maze (Floresco et al., 1997), place and
object-in-place recognition memory (Barker and Warburton, 2011), and
spontaneous alternation (Lalonde, 2002; Stevens and Cowey, 1973).
Some studies have used other hippocampal-dependent tasks (e.g.,
context fear conditioning; Sobesky et al., 2014), but these studies did
not meet the other inclusion criteria. A number of studies have in-
vestigated the effects of diet on occasion-setting/conditioned inhibition
processes (e.g., hippocampal-dependent feature negative discrimina-
tion) but these either did not meet the inclusion criterion of diet ex-
posure duration (Kanoski et al., 2007, 2010), or were excluded for
splitting animals into diet-resistant and diet-prone obesity groups
(Davidson et al., 2013).
2.2. Database search
We used Pubmed and Proquest central databases (Appendix A) and
limited the search to papers published on or before June 30th 2018.
2.3. Screening for inclusion
The process of selecting papers for inclusion in the meta-analysis is
shown in Fig. 1. Papers were first screened for eligibility using in-
formation provided in the title and abstract. Full texts of papers that
passed the eligibility test were then screened by two reviewers to
confirm that they had in fact met the requirements for inclusion in the
meta-analysis. In instances where there was disagreement, a third party
would have been asked to decide whether an article reached the elig-
ibility criteria, but there was no such disagreement.
K.N. Abbott, et al.
Fig. 1. Flow chart showing the process of selecting articles for inclusion in the
meta-analyses.
2.4. Data collection
The two reviewers independently extracted data from studies that
met the eligibility criteria and recorded information about the animals,
diet manipulation, behavioral assays, outcomes measured, and results.
For studies where subject body weights were provided, growth charts
from Charles River Laboratories were used to confirm animals were at
least 4 weeks of age based on weights provided. For studies where there
was no statistically significant difference between control and diet an-
imals but insufficient statistical details were provided in the published
methods and supplementary material, the corresponding author was
contacted twice to provide these details. If details were not provided, a
nominal F- or t-value of 1 was used for the meta-analysis. Excluding
these results would have contributed to any publication biases towards
papers reporting statistically significant results. When the number of
animals used for statistical analysis was provided as a range rather a
single value, the lowest, most conservative numerical value of the range
was used for analysis of effect size. When a study had multiple test
points but did not report a main effect, the data from each individual
test point was included. For studies that compared multiple diet ma-
nipulations to a single control group, the values for the single control
group were used in each of the diet manipulation meta-analyses.
2.5. Data analysis
Data were analyzed using Comprehensive Meta-Analysis version 3
(CMA v3). The studies were organized by (1) type of diet (high fat, high
sugar, and high fat-high sugar) and (2) type of behavioral task (Morris
water maze, place recognition, radial arm maze, and spontaneous al-
ternation). The standardized mean difference (SMD), calculated as
Hedge’s g (Hedges, 1981) and weighted by sample size, was used to
measure the effects of diet and task. A random effects model was se-
lected due to differences across the studies in calories, percentage of
fats and sugars, and behavioral tests. Therefore, statistics measuring
heterogeneity are not reported. We did not run a subgroups meta-
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Neuroscience and Biobehavioral Reviews 107 (2019) 399–421
analysis because the division into subgroups by three diet conditions
and four task types had a high degree of variance in the number of
experiments (or datasets) included in each subgroup. Additionally, the
datasets in one subgroup were not all strictly independent from those in
another subgroup; some datasets included across subgroups used the
same control group for comparison (e.g., for studies that compared
multiple diet manipulations to a single control group, the values for the
single control group were used in each of the diet manipulation meta-
analyses). Regardless, we were not so much concerned with an omnibus
test result from a subgroups meta-analysis but rather with the magni-
tude of the effect size in each subgroup. Therefore, we ran separate
meta-analyses with a Bonferroni correction to control for the use of the
same data set across two analyses (by diet and by task), an alpha of
α = 0.025 was considered significant.
3. Results
3.1. Study selection
The initial search yielded 991 articles. After the removal of dupli-
cates, 797 articles were screened based on the title and abstract, and
717 were excluded. Of the remaining 80 articles reviewed in full text, a
further 39 were excluded as they did not meet inclusion criteria. Of
these articles, 14 had a diet manipulation longer than the eight weeks
prior to behavioral testing, nine did not include a spatial learning and
memory behavioral task, seven started diet manipulations in animals
younger than 4 weeks, two had transgenic subjects but no wild type
control, two involved drug manipulations but lacked a vehicle control,
two did not make statistical comparisons between groups, one had no
appropriate control diet condition, one assessed the effect of maternal
diet on offspring, and one was a review article.
3.2. Study characteristics
Across the 41 articles that met eligibility criteria (with some articles
comprising of multiple eligible experiments or datasets), there were a
total of 32 experiments that investigated the effect of a high fat diet
(Table 2), nine experiments investigated the effect of a high sugar diet
(Table 3), and 11 experiments investigated the effect of a diet high in
both fat and sugar (Table 4). The effect of diet on spatial learning and
memory was assessed via the use of: extra-maze cues to navigate in the
Morris water maze, radial arm maze, or radial arm water maze; spon-
taneous alternation in a T- or Y-maze; or via the use of novel object
location in recognition memory tasks. Twenty-two experiments used
the Morris water maze (Table 5), 13 used the place recognition task
(Table 6), six used the radial arm or radial arm water maze (Table 7),
and four used spontaneous alternation (Table 8).
3.2.1. High fat diet
A total of 674–706 rats and mice (control n = 335–351; high fat diet
n = 339–355) were used to assess the effect of a high fat diet intake. Of
the 32 studies, 13 used C57BL/6 J mice (Arnold et al., 2014; Ayabe
et al., 2018; Denver et al., 2018; Magnusson et al., 2015; Silva et al.,
2005; Spinelli et al., 2017; Thirumangalakudi et al., 2008; Valladolid-
Acebes et al., 2011, 2013; Wei et al., 2018; Xu et al., 2018), eight used
Wistar rats (Alzoubi et al., 2013a, 2013b, 2018; Boitard et al., 2014;
Gergerlioglu et al., 2016; Mirzaei et al., 2018; Pratchayasakul et al.,
2015; Silva et al., 2005), and six used Sprague-Dawley rats (Hargrave
et al., 2016; Jamshed et al., 2014; Liang et al., 2015; Pathan et al.,
2008; Scichilone et al., 2016; Woodie and Blythe, 2018). The remaining
studies used Swiss Albino mice (Moreira et al., 2014), ICR mice (Park
et al., 2018), SAMP-8 mice (Che et al., 2018), F344xBN F1 rats (Spencer
et al., 2017), and Long-Evans rats (Jurdak et al., 2008). All the animals
were males, except for Jamshed et al. (2014) who used males and fe-
males, and Pratchayasakul et al. (2015) who used only females.
A total of 53 dependent variables were extracted from the 32
 Table 2
Composition and energy density of experimental and control diets provided to animals to examine the effect of high fat diet (HFD) consumption on hippocampal-dependent learning and memory. (* = where provided;
w/w = weight / weight; kcal = kilocalories).
Author & Expt
Alzoubi et al (2013a) Expt 1
Alzoubi et al (2013b) Expt 1
Alzoubi et al (2018)
Arnold et al (2014)
Ayabe et al (2018)
Boitard et al (2014)
Che et al (2018)
Denver et al (2018)
Gergerlioglu et al (2016) Expt 1
Hargrave et al. (2016) Expt 1
Jamshed et al. (2014) Expt 1
405
Jurdak et al (2008)
Liang et al. (2015)
Magnusson et al (2015)
Mirzaei et al (2018)
Moreira et al (2014)
Pathan et al (2008)
Pratchayasakul et al (2015)
Park et al (2018)
Scichilone et al (2016)
Silva et al. (2005)
Spencer et al (2017)
Spinelli et al (2017)
Thirumangalakudi et al (2008)
Valladolid-Acebes et al (2011)
Species & Strain [sex] Experimental diet [Energy Density*] Experimental diet Label from Fat Content Protein Control Diet [Energy Density*]
K.N. Abbott, et al.
Authors
Wistar rats [Male] Formulated diet (Sahil-Huran Animal Food Western Diet 25% (w/w) total fat including 18% (w/w) Standard diet (Sahil-Huran Animal
Company, Jordan) 11% (w/w) Unsat fat Food Company)
Wistar rats [Male] Formulated diet (Sahil-Huran Animal Food High Fat Cholesterol Diet 25% (w/w) total fat including 18% (w/w) Standard diet (Sahil-Huran Animal
Company, Jordan) 11% (w/w) Unsat fat Food Company)
Wistar rats [Male] Formulated diet (Unknown supplier) HFD 25% (w/w) total fat including 18% (w/w) Standard diet (Sahil-Huran Animal
11% (w/w) Unsat fat Food Company)
C57BL/6 J mice [Male] Research Diets #D12492 [5.21 kcal/g] Extreme HFD 60% kcal 20% kcal Research Diets Low-Fat Rodent Diet
#D12450B [3.82 kcal/g]
Research Diets #D12451 [4.7 kcal/g] Moderate HFD 45% kcal 20% kcal Research Diets Low-Fat Rodent Diet
#D12450B [3.82 kcal/g]
C57BL/6 J mice [Male] Research Diets #D12492 [5.21 kcal/g] HFD 60% kcal (30% w/w Lard) 20% kcal Research Diets Low-Fat Rodent Diet
#D12450 J [3.85 kcal/g]
Wistar rats [Male] Research Diets #D12451 [4.7 kcal/g] HFD 24% (w/w) – Standard chow A04 SAFE (Augy,
France) [2.9 kcal/g]
SAMP8 mice [Male] OpenSource Diets #D12492 HFD 18.4% (w/w) Lard + 4.6% 14% OpenSource Diets Low Fat Chow
(w/w) Corn Oil #D12450
C57BL/6 J mice [Male] Special Diet Services (Witham, UK) HFD 45% (w/w) fat – Standard chow (Harlan UK Ltd)
Wistar rats [Male] Formulated diet (Nukleon Ltd., Ankara, HFD 35% kcal from suet – Standard rat chow
Turkey)
Sprague Dawley rats Research Diets #D06040601 [6.1 kcal/g] Ketogenic Diet 80% kcal 15% Standard chow (Harlan Teklad)
[Male] [3.3 kcal/g]
Sprague Dawley rats Diets made from store bought ingredients by Cholesterol-Chocolate-Butterfat 5% (w/w) Butter-fat & 2% (w/ – Standard chow
[Male & Female] authors (CCB) diet w) Cholesterol
Long–Evans rats [Male] Purina chow [3.6 kcal/g] with partially- HFD 9.0 kcal/g – Purina chow [3.6 kcal/g]
hydrogenated fat (traditional Crisco) [9.0 kcal/
g]
Sprague Dawley rats Formulated diet (Anlimo Technology, China) HFD 40% total kcal – Standard chow (Anlimo Technology)
[Male]
C57BL/6 J mice [Male] Harlan Laboratories #TD.88137 [4.5 kcal/g] HFD 42% kcal 17.3% kcal PicoLab Rodent Diet #20 (LabDiet)
[4.07 kcal/g]
Wistar rats [Male] Royal Laboratory #D12492 [5.21 kcal/g] HFD 60% kcal 20% kcal Standard chow
Swiss Albino mice [Male] Chow is produced at the Universidade Estadual Hypercholestermic Diet 20% (w/w) Saturated fat + – Nuvilab-CR1 non-purified diet
de Campinas, Campinas, SP, Brazil 1.25% (w/w) Cholesterol
Sprague Dawley rats High fat pellet diet (Pranaw Agro Industries, HFD 58% total kcal 25% Standard chow diet (Pranaw Agro
[Male] New Delhi) Industries, New Delhi) [64 kcal/day]
Wistar rats [Male] Diet containing fat, mostly from lard HFD 59.28% total kcal (Lard) 26.45% C.P . Company #CP 082 Standard
[5.35 kcal/g] laboratory diet
ICR mice [Male] AIN-76A [3.77 kcal/g] + 40% beef Tallow No. HFD 40% (w/w) Beef Tallow – Standard Chow AIN-76A No. 100,000
101556 (Dyets Inc.) (Dyets Inc.) [3.77 kcal/g]
Sprague Dawley rats Bio-Serv #F5155 supplemented with 14% Ketogenic Diet 73.5% (w/w) 14% Standard chow
[Male] protein
Wistar rats [Male] – Ketogenic Diet 69% (w/w) 24% Nuvilab-CR1non-purified diet
F344xBN F1 rats [Male] Teklands Diets #TD.06414 [5.1 kcal/g] HFD 60.3% total kcal 18% Teklad Diets Standard chow #TD. 8640
[3.0 kcal/g]
C57BL/6 J mice [Male] Diets obtained from Mucedola (Italy) HFD 60% total kcal from saturated – Standard chow
fatty acids
C57BL/6 mice Tekland Diets HFD 21% Fat + 1.25% Cholesterol – –
C57BL/6 J mice [Male] Research Diets #D12451. [4.73 kcal/g] HFD 45% kcal (20% w/w Lard) 20% kcal Research Diets Low-Fat Rodent Diet
#D12450B [3.85 kcal/g]
(continued on next page)
Neuroscience and Biobehavioral Reviews 107 (2019) 399–421
 Table 2 (continued)
Author & Expt
Valladolid-Acebes et al (2013)
Expt 1
Valladolid-Acebes et al (2013)
Expt 3
Wei et al. (2018)
Woodie and Blythe (2018)
Xu et al. (2018)
406
Table 3
Composition and energy density of experimental and control diets provided to animals to examine the effect of high sugar diet (HSD) consumption on hippocampal-dependent learning and memory. (* = where
provided; w/w = weight / weight; kcal = kilocalories).
Author & Expt
Abbott et al (2016) Expt 1
Beilharz et al (2014) Expt 2
Gergerlioglu et al (2016)
Expt 1
Jurdak et al (2008)
Kendig et al (2013)
Magnusson et al. (2015)
Xu and Reichelt (2018)
Woodie and Blythe (2018)
Species & Strain [sex]
C57BL/6 J mice [Male]
C57BL/6 J mice [Male]
C57BL/6 J mice [Male]
Sprague Dawley rats
[Male]
C57BL/6 J mice [Male]
Species & Strain [sex]
Sprague Dawley rats [Male &
Female]
Sprague Dawley rats [Male]
Wistar rats [Male]
Long–Evans rats [Male]
Hooded Wistar rats [Male &
Female]
C57BL/6 J mice [Male]
Sprague Dawley rats [Male]
Sprague-Dawley rats [Male]
Experimental diet [Energy Density*] Experimental diet Label from Fat Content Protein Control Diet [Energy Density*]
Authors
K.N. Abbott, et al.
Research Diets #D12451. [4.73 kcal/g] HFD 45% kcal (20% w/w Lard) 20% kcal Standard chow
Research Diets #D12451. [4.73 kcal/g] HFD 45% kcal (20% w/w Lard) 20% kcal Standard chow
74% control diet and 10% lard compound HFD 5.28% (w/w) in CD + 10% 5% (w/w) Regular Diet
(Shanghai Pu Lu Teng Biological Technology) (w/w) Lard
Research Diets #D08060104 HFD 60% kcal – Harlan-Teklad Rat Chow #LM-485
Research Diets #D12492 [5.21 kcal/g] HFD 60% kcal – Standard diet
Experimental diet [Energy Density*] Experimental diet Label From Refined Sugar Content Protein Control Diet [Energy Density*]
Authors
Control diet [3.53 kcal/g] + 10% Sucrose HSD 0.4 kcal/g sucrose solution – Gordon’s Premium Rat and Mouse Breeder
solution [0.4 kcal/g] diet (Australia) [3.53 kcal/g]
Control diet [3.53 kcal/g] + 10% Sucrose HSD 0.4 kcal/g sucrose solution – Gordon’s Premium Rat and Mouse Breeder
solution [0.4 kcal/g] diet (Australia) [3.53 kcal/g]
Formulated diet (Nukleon Ltd., Ankara, Turkey) HSD 100% kcal of carbohydrate – Standard rat chow
from sucrose
Purina chow [3.6 kcal/g] + 32% Sucrose solution HSD 1.28 kcal/g sucrose solution – Purina chow [3.6 kcal/g]
[1.28 kcal/g]
Specialty Feeds Standard Chow [3.4 kcal/g] + HSD 0.4 kcal/g sucrose solution – Specialty Feeds Standard chow [3.4 kcal/g]
10% sucrose solution [0.4 kcal/g]
Harlan Laboratories # TD.98090 [4 kcal/g] HSD 66% (w/w) sucrose 17.7% kcal PicoLab Rodent Diet #20 [4.07 kcal/g]
Standard rat chow [2.63 kcal/g] + 10% sucrose HSD 0.4 kcal/g sucrose solution – Standard rat chow [2.63 kcal/g]
solution [0.4 kcal/g]
Research Diets #D05111802 High Fructose Diet 55% kcal – Standard chow
Neuroscience and Biobehavioral Reviews 107 (2019) 399–421

Table 4
Composition and energy density of experimental and control diets provided to animals to examine the effect of high fat-high sugar diet (HFHS) consumption on hippocampal-dependent learning and memory. (* =
where provided; w/w = weight / weight; kcal = kilocalories).
Author & Expt
Beilharz et al (2014) Expt 1
Beilharz et al (2014) Expt 2
Beilharz et al (2018)
Hargrave et al (2016) Expt
1 rats [Male]
407
Kanoski and Davidson
(2010)
Molteni et al (2004)
Ross et al (2013)
Takechi et al (2017)
Tran and Westbrook
(2015) Expt 1
Tran and Westbrook
(2018) Expt 1
Wu et al (2003) Expt 1
K.N. Abbott, et al.
Species & Strain Experimental diet [Energy Density*] Experimental diet Label Fat Content Refined Sugar Content Protein Control Diet [Energy Density*]
[sex] From Authors
Sprague Dawley Cafeteria diet consisting of store-bought "junk Cafeteria Diet with 45% (w/w) 0.4 kcal/g Sucrose solution; 5% Gordon’s Premium Rat and Mouse
rats [Male] foods" + 10% Sucrose Solution [0.4 kcal/g] Sucrose solution Unknown from solid diet Breeder diet (Australia) [3.53 kcal/g]
Sprague Dawley Cafeteria diet consisting of store-bought "junk Cafeteria Diet with 45% (w/w) 0.4 kcal/g Sucrose solution; 5% Gordon’s Premium Rat and Mouse
rats [Male] foods" + 10% Sucrose Solution [0.4 kcal/g] Sucrose solution Unknown from solid diet Breeder diet (Australia) [3.53 kcal/g]
Cafeteria diet consisting of store-bought "junk Cafeteria Diet 45% (w/w) Unknown 5%
foods"
Sprague Dawley Cafeteria diet consisting of store-bought "junk Cafeteria Diet with 45% (w/w) 0.4 kcal/g Sucrose solution; 5% Standard chow
rats [Male] foods" + 10% Sucrose Solution [0.4 kcal/g] Sucrose solution Unknown from solid diet
Sprague Dawley Harlan #TD.10768 [4.5 kcal/g] High-fat, high-dextrose 38% kcal 20% kcal Dextrose 24% Harlan Teklad Standard chow [3.3 kcal/
“Western” diet g]
Sprague Dawley Harlan Teklad Powered Diet #TD.04489 High Energy Diet 170 g/kg Lard 220.5 g/kg Glucose – Purina LabDiet #5001 [3.0 kcal/g]
rats [Male] [4.55 kcal/g]
Fisher 344 rats Powdered HFS diet (Purina Mills Inc., Test Diets HFHS 39% total kcal 40% total kcal from sucrose – Powdered low-fat, complex
[Female] Inc.) (primarily lard) carbohydrate diet (Purina Mills Inc.,
Test Diets Inc.)
Sprague Dawley Control diet, a petri dish containing animal lard HFHS Free access to Lard 32% Sucrose solution; – Purina LabDiet #5001 [3.0 kcal/g]
rats [Male] [9.0 kcal/g], and a bottle of 32% sucrose solution Unknown from solid diet
[1.13 kcal/g]
C57BL6/J mice Specialty Feeds #SF14-088 High Fat Fructose Diet 30% (w/w) Lard, 0.5% 15% (w/w) Fructose – Specialty Feeds Low-Fat chow #AIN-
[Male] (w/w) Cholesterol 93M
Sprague Dawley Cafeteria diet made of store-bought "junk foods" HFHS Diet 40% (w/w) Primarily 40% (w/w) Sucrose 5% Gordon’s Premium Rat and Mouse
rats [Male] lard Breeder diet (Australia) [3.53 kcal/g]
Sprague Dawley Cafeteria diet made of store-bought "junk foods" HFHS Diet 40% (w/w) Primarily 40% (w/w) Sucrose 5% Gordon’s Premium Rat and Mouse
rats [Male] lard Breeder diet (Australia) [3.53 kcal/g]
Sprague Dawley Powdered HFHS diet (Purina Mills Inc., Test Diets HFS Diet 39% total kcal 40% total kcal from sucrose – Powdered low-fat, complex
rats [Male] Inc.) (primarily lard) carbohydrate diet (Test Diets Inc.)
Neuroscience and Biobehavioral Reviews 107 (2019) 399–421
 Table 5
Experimental details and results for studies examining the effect of dietary manipulation on hippocampal-dependent learning and memory in the Morris water maze. (*Approximate age based on growth charts. When
multiple groups of diet manipulation lengths have been used: + = separate experimental groups; When multiple tests have been used: ^ = ongoing test without training between test sessions; # = isolated test involving
training and testing. CD = Control Diet; HFD = high fat diet; HFHS = high fat-high sugar diet; HSD = high sugar diet).
K.N. Abbott, et al.

Author & Expt Species & Strain [sex] Experiment Diet Age* at Diet Onset Diet Dependent Variable Results
Duration [Retention Interval]

Boitard et al (2014) Wistar rats [Male] HFD 12 weeks 2 months Number target crossings [2- Rats consuming HFD had an equivalent number of target crossings as
hr]^ control rats at both 2-hr and 4-day retention intervals.
Number target crossings [4
day]^
Che et al (2018) SAMP8 mice [Male] HFD 10 months old 8 weeks Time in target quadrant [24- Mice consuming HFD spent significantly less time in the target quadrant
hr] than control mice
Denver et al (2018) C57BL/6 J mice [Male] HFD 7-14 weeks 10 days+ Time in target quadrant [24- Rats consuming the HFD did not significantly differ from rats consuming
26 days+ hr] CD, however the time in target quadrant for both groups did not
8 weeks+ significantly differ from chance.
Gergerlioglu et al (2016) Wistar rats [Male] HFD 10–12 weeks 3 weeks Time in target quadrant [24- Rats consuming HFD spent significantly less time in the target quadrant
Expt 1 hr] than rats consuming CD.
HSD 10–12 weeks 3 weeks Time in target quadrant [24- There was no effect of diet on time spent in the target quadrant.
hr]
Jamshed et al (2014) Expt Sprague Dawley rats HFD (labelled cholesterol- 6+ weeks* (180- 6 weeks Escape latency [24-hr] Rats consuming the CCB diet took significantly longer to reach the escape
1 [Male & Female] chocolate-butterfat diet by 200 grams) platform than rats consuming CD.
authors)
Jurdak et al (2008) Long–Evans rats [Male] HFD 6 weeks 5 weeks Time in target quadrant [24- There was no effect of diet on time spent in the target quadrant at 24-hrs or
hr]^ 10-days post-training.
Time in target quadrant [10
day]^
HSD 6 weeks 5 weeks Time in target quadrant [24- Rats consuming the HSD spent equivalent time in the target quadrant as
hr]^ rats consuming CD when tested 24-hrs after training, however spent

408
Time in target quadrant [10
day]^
Kendig et al (2013) Hooded Wistar rats [Male HSD 4 and 8 weeks 4 weeks Time in target quadrant
& Female] (Probe tests 1 -3) [24-hr]^
Time in target quadrant [28
day]^
Liang et al. (2015) Sprague Dawley rats HFD 6 weeks 6 weeks Time in target quadrant [24-
[Male] hr]
Magnusson et al. (2015) C57BL/6 J mice [Male] HFD 8 weeks 5 weeks Proximity from platform
(Probe 1) [1-hr]#
Proximity from platform
(Probe 2) [1-hr]#
Proximity from platform
(Probe 3) [1-hr]#
Proximity from platform
(Probe 4) [1-hr]#
Reversal Task [1-hr]
HSD Proximity from platform
(Probe 1) [1-hr]#
Proximity from platform
(Probe 2) [1-hr]#
Proximity from platform
(Probe 3) [1-hr]#
Proximity from platform
(Probe 4) [1-hr]#
significantly less time in the target quadrant than control rats when tested
10-days after training.
During the first three probe trials, rats consuming HSD spent significantly
less time in the target quadrant than rats consuming CD.
Rats consuming HSD spent less time in the target quadrant than rats
consuming CD, however this difference was not significant.
Rats consuming HFD spent significantly less time in the target quadrant
than rats consuming CD.
Rats consuming HFD had greater proximity from platform location than
control rats, however this difference was not significant.
Rats consuming HFD had greater proximity from platform location than
control rats, however this difference was not significant.
Rats consuming HFD had greater proximity from platform location than
control rats, however this difference was not significant.
Rats consuming HFD had a smaller proximity from platform location than
rats consuming chow, however this was not significant.
Proximity from new platform location did not differ between HFD and CD
rats; HFD had significantly smaller proximity to old platform location than
CD rats.
Rats consuming HSD had greater proximity from platform location than
control rats, however this was not significant.
No effect of diet on proximity from platform, with rats in both groups
having a similar distance from the platform location.
Rats consuming HSD had a smaller proximity from platform location than
control rats, however this was not significant.
Rats consuming HSD had a smaller proximity from platform location than
control rats, however this was not significant.
(continued on next page)
Neuroscience and Biobehavioral Reviews 107 (2019) 399–421
 Table 5 (continued)
Author & Expt
Mirzaei et al (2018)
Molteni et al (2004)
Pathan et al (2008)
Pratchayasakul et al (2015)
Scichilone et al (2016)
Silva et al (2005)
Spencer et al (2017)
Spinelli et al (2017)
Takechi et al (2017)
Wei et al (2018)
409
Woodie and Blythe (2018)
Wu et al (2003) Expt 1
Xu et al (2018)
Species & Strain [sex] Experiment Diet Age* at Diet Onset Diet Dependent Variable Results
Duration [Retention Interval]
K.N. Abbott, et al.
Reversal Task [1-hr] Proximity from new platform location did not differ between HSD and CD
rats; HSD had significantly smaller proximity to old platform location than
CD rats.
Wistar rats [Male] HFD 8 Weeks 8 weeks Time in target quadrant [24- Rats consuming a HFD spent significantly less time in the target quadrant
hr] than rats consuming CD.
Fisher 344 rats [Female] Powdered HFHS 8 weeks 2 months Time in target quadrant [3 Rats consuming HFHS diet spent equal time in all four MWM quadrants at
day] test; time in target quadrant was significantly lower than that of CD rats.
Sprague Dawley rats HFD 5+ weeks* (150- 5 weeks Escape latency [24-hr] Decrease in escape latency across the five days of training was significantly
[Male] 190 grams) greater in rats consuming CD than rats consuming HFD.
Wistar rats [Female] HFD 8+ weeks* (200- 4 weeks+ Time in target quadrant [24- There was no effect of diet on time in target quadrant.
220 grams) hr]
8 weeks+ Time in target quadrant [24- There was no effect of diet on time in target quadrant.
hr]
Sprague Dawley rats Ketogenic Diet 4 weeks 8 weeks Time in target quadrant [2- Rats consuming the ketogenic diet spent less time in the target quadrant
[Male] hr] than control rats, however this was not significant.
Wistar rats [Male] Ketogenic Diet 30 days old 40 days Time in target quadrant [24- Rats consuming the ketogenic diet spent less time in the target quadrant
hr] than control rats, however this was not significant.
F344xBN F1 rats [Male] HFD 3-months+ 4 days Time in target quadrant [4 There was no effect of diet on time spent in the target quadrant.
24-months+ day] There was no effect of diet on time spent in the target quadrant.
C57BL/6 J mice [Male] HFD 30-35 days 6 weeks Time in target quadrant [24- Mice consuming HFD spent significantly less time in the target quadrant
hr] than control mice.
C57BL6/J mice [Male] High Fat Fructose Diet (or 6 weeks 4 weeks Escape latency [24 -hr] Mice consuming HFF diet had a slower latency to the platform than mice
HFHS) consuming CD, however this was not significant.
C57BL/6 J mice [Male] HFD 12-14 months 8 Weeks Time in target quadrant [24- HFD mice spent less time in the target quadrant than mice consuming CD.
hr]
Sprague Dawley rats HFD 6 weeks 8 weeks Time in target quadrant [24- There was no effect of diet on the time spent in the target quadrant during
[Male] hr] probe test.
Reversal Task Time in target There was no effect of diet on time spent in new target quadrant.
quadrant [24-hr]
High Fructose Diet (or HSD) Time in target quadrant [24- There was no effect of diet on the time spent in the target quadrant during
hr] probe test.
Reversal Task Time in target There was no effect of diet on time spent in new target quadrant.
quadrant [24-hr]
Sprague Dawley rats Powdered HFHS 6+ weeks* (200- 4 weeks Time in target quadrant [4- There was no effect of diet on time spent in the target quadrant.
[Male] 240 grams) hr]
C57BL/6 J mice [Male] HFD 4 Weeks 8 weeks Time in target quadrant [24- HFD spent significantly less time in the target quadrant than mice
hr] consuming CD.
Neuroscience and Biobehavioral Reviews 107 (2019) 399–421
K.N. Abbott, et al.
experiments (some studies conducted multiple tests within a single
experiment) for inclusion in the analysis. Experimental animals were
provided ad libitum access to a formulated high fat diet obtained from a
local manufacturer, except for Jamshed et al. (2014) who used a diet
consisting of store-bought foods, and Jurdak et al. (2008) and Wei et al.
(2018) who used control chow mixed with partially-hydrogenated fat
or lard, respectively.
3.2.2. High sugar diet
A total of 241 rats and mice (control n = 117; high sugar diet
n = 124) were used to assess the effect of a high sugar diet intake. Of
the nine experiments, four used Sprague-Dawley rats (Abbott et al.,
2016; Beilharz et al., 2014; Kendig et al., 2013; Xu and Reichelt, 2018),
two used C57BL6 J mice (Magnusson et al., 2015), one used Wistar rats
(Gergerlioglu et al., 2016), one used hooded Wistar rats (Kendig et al.,
2013), and one used Long Evans rats (Jurdak et al., 2008). All experi-
ments used male subjects, with the exception of Abbott et al. (2016)
and Kendig et al. (2013) who used male and female rats.
A total of 18 dependent variables were extracted from the nine
experiments for inclusion in the analysis. Experimental animals were
provided a 10% sucrose solution ad libitum (Beilharz et al., 2014;
Jurdak et al., 2008) or in a 2 -hour daily access period (Abbott et al.,
2016; Kendig et al., 2013; Xu and Reichelt, 2018), a 32% sucrose so-
lution with ad libitum access (Jurdak et al., 2008), or a semi-purified
rodent chow with a high sugar content (Gergerlioglu et al., 2016;
Magnusson et al., 2015; Woodie and Blythe, 2018).
3.2.3. High fat-high sugar diet
A total of 303 rats and mice (control n = 155; high fat-high sugar
diet n = 148) were used to assess the effect of a high fat-high sugar diet.
Of the 11 experiments, nine used Sprague-Dawley rats (Beilharz et al.,
2014, 2018; Hargrave et al., 2016; Kanoski and Davidson, 2010; Ross
et al., 2013; Tran and Westbrook, 2015, 2018; Wu et al., 2003), one
used C57BL/6 J mice (Takechi et al., 2017), and one used F344 rats
(Molteni et al., 2004). All experiments used male subjects, with the
exception of Molteni et al (2004) who used female rats.
A total of 13 dependent variables were extracted from 11 experi-
ments for inclusion in the analysis. Experimental animals were pro-
vided ad libitum access to a formulated high fat-high sugar diet in
pelleted (Hargrave et al., 2016; Takechi et al., 2017) or powdered
(Kanoski and Davidson, 2010; Molteni et al., 2004; Wu et al., 2003)
form, a diet consisting of chow supplemented with store-bought foods
(Beilharz et al., 2014, 2018; Tran and Westbrook, 2015, 2018), or chow
supplemented with lard and a bottle of 32% sucrose solution (Ross
et al., 2013).
3.2.4. Morris water maze
A total of 531–544 (control n = 258–266; experimental diet
n = 273–278) animals were used to assess the effect of dietary intake
on spatial memory using the Morris water maze. Of the 22 experiments,
five examined the effect of a high sugar diet (Gergerlioglu et al., 2016;
Jurdak et al., 2008; Kendig et al., 2013; Magnusson et al., 2015; Woodie
& Blythe, 2018), 18 examined the effect of high fat diet, and three
examined the effect of high fat-high sugar diet (Molteni et al., 2004;
Takechi et al., 2017; Wu et al., 2003). All experiments used male sub-
jects, except for Jamshed et al. (2014) and Kendig et al. (2013) who
used male and female rats, and Molteni et al. (2004) and
Pratchayasakul et al. (2015) who used female rats.
Thirty-nine dependent variables were extracted from the 22 ex-
periments for inclusion in the analysis. All of the experiments used time
in target quadrant as their dependent variable of spatial memory, ex-
cept for those reported by Boitard et al. (2014), which used number of
target crossings, Magnusson et al. (2015), which used proximity from
platform location, and, finally, by Jamshed et al. (2014); Pathan et al
(2008), and Wei et al (2018) which all used escape latency.
410
Neuroscience and Biobehavioral Reviews 107 (2019) 399–421
3.2.5. Place recognition
A total of 391–394 (control n = 189–190; experimental diet
n = 202–204) animals were used to assess the effect of dietary intake
on spatial memory using the place recognition task. Of the 13 experi-
ments, four examined the effect of a high sugar diet provided ad libitum
(Beilharz et al., 2014; Magnusson et al., 2015) or 2 -hour restricted
access (Abbott et al., 2016; Xu and Reichelt, 2018), five examined the
effect of high fat diet (Ayabe et al., 2018; Magnusson et al., 2015;
Moreira et al., 2014; Valladolid-Acebes et al., 2011, 2013), and five
examined a high fat-high sugar diet (Beilharz et al., 2014, 2018; Ross
et al., 2013; Tran and Westbrook, 2015, 2018). All experiments used
male subjects, with the exception of Abbott et al. (2016) who used male
and female rats.
Twenty-one dependent variables were extracted from the 13 ex-
periments for inclusion in the analysis. All of the experiments assessed
spatial memory using a score to quantify the difference in time spent
exploring the object in a novel location compared with the time spend
exploring the object in a familiar location. The exact formula for cal-
culating the memory score sometimes differed between studies (e.g.,
novelty proportion vs discrimination ratio), but more time spent ex-
ploring the novel location was always taken to index better recognition
memory.
3.2.6. Radial arm or radial arm water maze
A total of 147–153 (control n = 72–75; experimental diet
n = 75–78) animals were used to assess the effect of dietary intake on
spatial memory using either the radial arm or radial arm water-maze
task. Of the six experiments, five examined the effect of high fat diet
intake (Alzoubi et al., 2013a, 2013b, 2018; Thirumangalakudi et al.,
2008; Valladolid-Acebes et al., 2011) and one examined the effect of
high fat-high sugar diet intake (Kanoski and Davidson, 2010). All ex-
periments used male subjects.
Thirteen dependent variables were extracted from the six experi-
ments for inclusion in the analysis. All experiments assessed spatial
memory by measuring the total sum of working memory errors, defined
as re-entry into an arm that previously contained a reward or platform,
and reference memory errors, defined as entry or re-entry an arm that
has never contained a reward or platform; two experiments evaluated
total errors in addition to working memory errors separately
(Thirumanagalakudi et al., 2008; Valladolid-Acebes et al., 2011).
3.2.7. Spontaneous alternation
A total of 76 (control n = 43; experimental diet n = 33) animals
were used to assess the effect of diet on spatial memory using sponta-
neous alternation in either a T- (Arnold et al., 2014) or Y-maze
(Hargrave et al., 2016; Park et al., 2018). All four experiments ex-
amined the effect of a high fat diet (Arnold et al., 2014; Hargrave et al.,
2016; Park et al., 2018), and one additionally examined the effect of
high fat-high sugar diet (Hargrave et al., 2016). All experiments used
male subjects.
A total of seven dependent variables were extracted from the four
experiments for inclusion in the analysis. One experiment assessed
spatial memory by measuring the percentage of sequential arm entries
(Hargrave et al., 2016), and the remaining three examined the number
of entries into a new arm in the T- or Y-maze.
3.3. Meta-analysis output
The forest plots and individual statistics for the diets high in fat,
sugar, and both fat and sugar are shown in Figs. 2–4, respectively.
There was a significant overall negative effect of consuming a diet high
in fat (k = 53, g = -0.595, 95% CI [-0.715 – -0.474], p < .001), re-
fined sugar (k = 18, g = -0.552, 95% CI [-0.750 – -0.355], p < .001),
or both fat and refined sugar (k = 13, g = -0.654, 95% CI [-0.882 –
-0.426], p < .001), on hippocampal-dependent spatial learning and
memory. Each diet had a medium effect size.
 Table 6
Experimental details and results for studies examining the effect of dietary manipulation on hippocampal-dependent learning and memory in the place recognition task. (*Approximate age based on growth charts. When
multiple groups of diet manipulation lengths have been used: + = separate experimental groups; When multiple tests have been used: ^ = ongoing test without training between test sessions; # = isolated test involving
training and testing. CD = control diet; HFD = high fat diet; HFHS = high fat-high sugar diet; HSD = high sugar diet).
Author & Expt Species & Strain Experiment Diet Age* at Diet Onset Diet Behavioural Task Results
K.N. Abbott, et al.

(sex) Duration [Retention Interval]

Abbott et al (2016) Expt 1 Sprague Dawley rats HSD 4 weeks 2 weeks Place Recognition [5- Male and female HSD rats spent a significantly smaller proportion of time
[Male & Female] min] exploring the novel object location than control rats.
3 weeks Object-in-Place Male HSD rats spent a significantly smaller proportion of time exploring the
Recognition [5-min] objects in the novel locations than male control rats. There was no effect of
HSD on exploration of objects in female rats.
Ayabe et al (2018) C57BL/6 J mice HFD 6 Weeks 7 Weeks Place Recognition [4- HFD rats spent a smaller proportion of time exploring the novel object
[Male] hr] location then control mice, however this was not significant.
Beilharz et al (2014) Expt 1 Sprague Dawley rats HFHS (labelled Cafeteria Diet with 8+ weeks* (363- 5-6 days Place Recognition [5- Main effect of diet, such that rats consuming cafeteria diet with sucrose
[Male] Sucrose solution by authors) 463 grams) min]# solution spent a significantly smaller proportion of time exploring the novel
11-12 days Place Recognition [5- object location than control rats.
min]#
20 - 21 days Place Recognition [5-
min]#
Beilharz et al (2014) Expt 2 Sprague Dawley rats HSD 7+ weeks* 5-6 days Place Recognition [5- Main effect of diet, such that rats consuming the HSD, cafeteria diet, or the
[Male] (302–366 grams) min]# cafeteria diet with sucrose solution spent a significantly smaller proportion of
HFHS (labelled Cafeteria Diet with 11-12 days Place Recognition [5- time exploring the novel object location than control rats.
Sucrose solution by authors) min]#
HFHS (labelled Cafeteria Diet with 20 - 21 days Place Recognition [5-
Sucrose solution by authors) min]#
Beilharz et al (2018) Sprague Dawley rats HFHS (labelled Cafeteria Diet with 5+ weeks* (200 grams) 10-11 days Place Recognition [5- Main effect of diet, such that rats consuming cafeteria diet with sucrose
[Male] Sucrose solution by authors) min]# solution spent a significantly smaller proportion of time exploring the novel
17-18 days Place Recognition [5- object location than control rats.
min]#

411
Magnusson et al (2015) C57BL/6 J mice HFD 8 weeks 2 weeks Place Recognition [1- There was no significant effect of diet on proportion of time spent exploring
[Male] hr]^ the object in the novel object location, however exploration did not occur
Place Recognition [24- above chance for either HFD or CD animals.
hr]^
HSD 8 Weeks 2 Weeks Place Recognition [1- There was no significant effect of diet on proportion of time spent exploring
hr]^ the object in the novel object location, however exploration did not occur
Place Recognition [24- above chance for either HSD or CD animals.
hr]^
Moreira et al (2014) Swiss Albino mice HFD (labelled Hypercholestermic Diet 3 months old 8 weeks Place Recognition [90- Mice consuming a hypercholesterolemic diet spent a significantly smaller
[Male] by authors) min] proportion of time exploring the novel object location than control mice.
Ross et al (2013) Sprague Dawley rats HFHS 7-8 weeks 4 weeks Place Recognition [24- There was no effect of diet on the proportion of time spent exploring the
[Male] hr] novel object location.
Tran and Westbrook (2015) Sprague Dawley rats HFHS 5+ weeks* (200- 1 week Place Recognition [5- Main effect of diet, such that rats consuming HFHS diet spent a significantly
Expt 1 [Male] 300 grams) min]# smaller proportion of time exploring the novel object location than control
2 week Place Recognition [5- rats.
min]#
3 week Place Recognition [5-
min]#
Tran and Westbrook (2018) Sprague Dawley rats HFHS 5+ weeks* (200- 1 week Place Recognition [5- Rats consuming HFHS diet spent a significantly smaller proportion of time
Expt 1 [Male] 300 grams) min] exploring the novel object location than control rats
Valladolid-Acebes et al C57BL/6 J mice HFD 5 weeks 8 weeks Place Recognition [1- Mice consuming HFD spent a significantly smaller proportion of time
(2013) Expt 1 [Male] hr]^ exploring the novel object location than control mice tested 1-hr and 24 -hrs
Place Recognition [24- post-training.
hr]^
Valladolid-Acebes et al C57BL/6 J mice HFD 8 weeks 8 weeks Place Recognition [1- There was no effect of diet on proportion of time spent exploring the novel
(2013) Expt 3 [Male] hr]^ object location when tested 1-hr following training; HFHS diet mice spent a
Place Recognition [24- smaller proportion of time exploring the novel object location at 24-hr test,
hr]^ however this difference was not significant.
Xu and Reichelt (2018) Sprague Dawley rats HSD 4 weeks 3 weeks Place Recognition [5- HSD rats spent a significantly smaller proportion of time exploring the novel
[Male] min] object location than control rats.
Neuroscience and Biobehavioral Reviews 107 (2019) 399–421
K.N. Abbott, et al.
The forest plots and individual statistics for the Morris water maze,
place recognition task, radial arm mazes, and spontaneous alternation
tasks are shown in Figs. 5–8, respectively. There was a significant
overall negative effect of consuming a diet high in fat, sugar, or high in
both fat and sugar, on performance in the Morris water maze (k = 43, g
= -0.375, 95% CI [-0.511 – -0.239], p < .001), place recognition task
(k = 21, g = -0.759, 95% CI [-0.939 – -0.578], p < .001), radial arm
or radial arm water maze (k = 13, g = -0.932, 95% CI [-1.153 –
-0.710], p < .001), and spontaneous alternation (k = 7, g = -0.557,
95% CI [-0.894 – -0.219], p < .01). The effect of diet on behavioral
performance was a medium effect size for all tasks except for the radial
arm maze where the effect size was large.
4. Discussion
There is considerable evidence that rodents fed a diet high in fat,
sugar, or both fat and sugar exhibit impairments in tasks assessing
hippocampal-dependent forms of learning and memory (Kanoski et al.,
2010; Yeomans, 2017). However, there have been failures to detect
such impairments (e.g., Ayabe et al., 2018; Ross et al., 2013, Jurdak
et al., 2008). One source of the inconsistent results is the type of diet
used, while a second source is the type of task used to assess the effects
of the diet. Therefore, we subjected this evidence to a meta-analysis in
order to provide a quantitative assessment of the protocols under which
dietary manipulations adversely affect hippocampal-dependent forms
of cognition. We had two aims: The first was to assess the contribution
of diets high in saturated fat, refined sugar, or both, to impairments of
spatial learning and memory. The second aim was to examine the tasks
used to determine whether they differed in their sensitivity to the
dietary manipulations.
4.1. Summary of results
The meta-analysis revealed that all three diet manipulations pro-
duce a significant impairment in spatial learning and memory tasks,
relative to a control diet that is usually starch based and low in satu-
rated fats and refined sugars. While direct statistical comparisons be-
tween the diet manipulation categories were not permitted, the size of
the Hedge’s g for the three manipulations suggests that the largest effect
size was found for studies that used a diet high in both fat and sugar,
followed closely by studies using a high fat diet, and, finally, a high
sugar diet. Nonetheless, all three dietary manipulations were observed
to have a medium effect size, which suggests that differences in dietary
composition are unlikely to be the single or primary factor responsible
for the inconsistent findings in the literature.
A second source of variability in the findings reported is the beha-
vioral task used to assess dietary effects on learning and memory. As
noted in the Introduction, tasks assessing hippocampal forms of cog-
nition, specifically, spatial learning and memory, appear to be espe-
cially sensitive to dietary manipulations. The role of the hippocampus
in successful performance on the tasks selected for inclusion in the
meta-analysis has been well documented: the Morris water maze (e.g.,
Compton et al., 1997), place recognition (e.g., Barker and Warburton,
2011), radial arm and radial arm water maze (e.g., Floresco et al.,
1997), spontaneous alternation (e.g., Lalonde, 2002). When the per-
formance of animals consuming a diet high in saturated fat, refined
sugar, or both, on these tasks were considered separately, the meta-
analysis revealed a significant diet-induced impairment in spatial
learning and memory for each task group. Again, direct statistical
comparisons between the behavioral tasks was not permitted. However,
the largest impairment was seen on the radial arm and radial water
maze tasks, where there was a large effect size, followed by the place
recognition task, the spontaneous alternation task, and the Morris water
maze task, each of which had a medium effect size. It should be noted
that nearly half of the experiments included in the meta-analysis for the
radial arm maze and radial water maze tasks were extracted from two
412
Neuroscience and Biobehavioral Reviews 107 (2019) 399–421
papers (Alzoubi et al., 2013a; and 2013b), which may have biased the
results. However, the weighted effect sizes of the six dependent mea-
sures extracted from these two papers were among the smaller effect
sizes in the analysis, suggesting that the large SMD observed for this
task group does not rely on their inclusion in the analysis.
The role of the hippocampus in successful performance on spatial
learning and memory tasks is well established (Barker and Warburton,
2011; Compton et al., 1997; Floresco et al., 1997; Lalonde, 2002), but
studies differed in the procedures used in these tasks. Moreover, var-
iations in how these tasks are implemented may affect the degree to
which the hippocampus is recruited. For example, studies that used the
Morris water maze differed in terms of the number of training days, the
number of training trials per day, the inter-trial and inter-training day
intervals, and the retention interval before test. Similarly, there were
differences across studies in the place recognition task, such as the
number of objects used, the length of familiarization time, the retention
interval before test, and the arena where the task was conducted.
Procedural variations in these tasks, particularly in the amount of
training, length of retention interval, and maze set-up (affecting the
amount of extra-maze spatial information that can be extracted), have
been argued to affect the involvement of brain regions outside the
hippocampus (e.g., Tran and Westbrook, 2017; Vorhees and Williams,
2006, 2014; see Tran and Westbrook, 2018 for discussion in relation to
object recognition memory). Thus, such variations may have affected
the difficulty of the task; increasing or decreasing the reliance on a
functioning hippocampus for successful performance. Moreover, the
effects of diet on learning and memory can be highly specific, impairing
some, but not other, similar tasks (e.g., Hargrave et al., 2016; Tran and
Westbrook, 2015). Therefore, the inconsistencies in the literature on
the observed relationship between diet and cognition are likely a con-
sequence of procedural difference in the assessment measure rather
than the content of dietary manipulation.
4.2. Rodent species as a variable for diet-induced cognitive impairment
Rats and mice, as well as different strains within these species, can
perform differently on hippocampal-dependent behavioral tasks (e.g.
Cressant et al., 2007; Ennaceur et al., 2005; Genzel et al., 2017;
Stranahan, 2011; reviewed in Hok et al., 2016; Keeley et al., 2015).
Such differences are thought to be due to variations in metabolism
(Chang et al., 1990), hippocampal neurogenesis (Merritt and Rhodes,
2015), gene expression (Malki et al., 2015), brain volume (Keeley et al.,
2015), and place cell activity (Ji et al., 2018; see Manahan-Vaughan,
2019). These differences in turn could interact with dietary manipula-
tions to affect performance on hippocampal-dependent tasks (Buettner
et al., 2007; Stöckli et al., 2017; West et al., 1992, 1995). However, we
found little if any evidence for such effects based on the study de-
scriptives.
Of the 41 articles that were included in the present meta-analysis,
16 experiments were extracted from 14 articles examining dietary
manipulations in mice and 29 experiments were extracted from 27 ar-
ticles examining dietary manipulations in rats. Impairment in hippo-
campal-dependent learning and memory was observed in 10 experi-
ments (approximately 63%) using mice (Arnold et al., 2014; Che et al.,
2018; Moreira et al., 2014; Park et al., 2018; Spinelli et al., 2017;
Thirumangalakudi et al., 2008; Valladolid-Acebes et al., 2011, 2013,
Experiment 1; Wei et al., 2018; Xu et al., 2018) and 16 experiments
(approximately 55%) using rats (Abbott et al., 2016; Alzoubi et al.,
2013a, 2013b, 2018; Beilharz et al., 2014; Kanoski and Davidson, 2010;
Liang et al., 2015; Mirzaei et al., 2018; Molteni et al., 2004; Pathan
et al., 2008; Tran and Westbrook, 2015, 2018; Xu and Reichelt, 2018);
no deficits were observed in five experiments using mice (Ayabe et al.,
2018; Denver et al., 2018; Magnusson et al., 2015; Takechi et al., 2017)
and nine experiments using rats (Boitard et al., 2014; Jamshed et al.,
2014; Pratchayasakul et al., 2015; Ross et al., 2013; Scichilone et al.,
2016; Silva et al., 2005; Spencer et al., 2017; Woodie and Blythe, 2018;

Table 7
Experimental details and results for studies examining the effect of dietary manipulation on hippocampal-dependent learning and memory in the radial arm maze (RAM) or radial arm water maze (RAWM).
(*Approximate age based on growth charts. When multiple groups of diet manipulation lengths have been used: + = separate experimental groups; When multiple tests have been used: ^ = ongoing test without training
between test sessions; # = isolated test involving training and testing. CD = control diet; HFD = high fat diet; HFHS = high fat-high sugar diet; HSD = high sugar diet; RM = reference memory; WM = working
memory;).
Author & Expt
Alzoubi et al (2013a) Expt 1
Alzoubi et al (2013b) Expt 1
413
Alzoubi et al (2018)
Kanoski and Davidson (2010)
Thirumangalakudi et al
(2008)
Valladolid-Acebes et al.
(2011)
K.N. Abbott, et al.
Species & Strain Experimental Diet Age* at Diet Onset Diet duration Behavioural Task (Dependent Results
[sex] Variable) [Retention Interval]
Wistar rats HFD (labelled Western Diet by 6-7 weeks 6 weeks Radial 6-arm water maze (WM & Rats consuming the western diet made significantly more incorrect
[Male] authors) RM errors) [30-min]^ arm entries than rats consuming control diet when tested 30-min, 5 -
Radial 6-arm water maze (WM & hrs, and 24 -hrs post-training
RM errors) [5-hr]^
Radial 6-arm water maze (WM &
RM errors) [24-hr]^
Wistar rats HFD (labelled High Fat 6-7 weeks 6 weeks Radial 6-arm water maze (WM & Rats consuming the HFCD made significantly more incorrect arm
[Male] Cholesterol Diet by authors) RM errors) [30-min]^ entries than rats consuming control diet when tested 30-min, 5 -hrs,
Radial 6-arm water maze (WM & and 24 -hrs post-training.
RM errors) [5-hr]^
Radial 6-arm water maze (WM &
RM errors) [24-hr]^
Wistar rats HFD 4+ weeks* 4 weeks Radial 6-arm water maze (WM & Rats consuming the HFD made significantly more incorrect arm
[Male] (160–200 grams) RM errors) [5-hr]^ entries than rats consuming control diet when tested 5 -hrs and 24 -
Radial 6-arm water maze (WM & hrs post-training.
RM errors) [24-hr]^
Sprague Dawley HFHS (labelled High Energy 8-9 weeks 6 tests starting Radial Arm Maze (WM & RM Rats consuming the high energy diet made significantly more
rats [Male] Diet by authors) at 3 days errors) [training prior to diet incorrect arm entries than control rats.
access]
C57BL/6 mice HFD 4 months old 2 months Radial 8-Arm Water Maze (WM Mice consuming HFD made significantly more entries into an arm
Errors) [24-hrs] that previously contained a platform than mice consuming CD.
Radial 8-Arm Water Maze (WM & Mice consuming the HFD made significantly more incorrect arm
RM errors) [same test] entries than mice consuming tCD.
C57BL/6 J mice HFD 4 weeks old 8 weeks Radial arm maze (WM errors) [24- Mice consuming HFD made significantly more entries into a
[Male] hrs] previously baited arm than mice consuming CD.
Radial arm maze (WM & RM Mice consuming the HFD made significantly more incorrect arm
errors) [same test] entries than mice consuming CD.
Neuroscience and Biobehavioral Reviews 107 (2019) 399–421
K.N. Abbott, et al. Neuroscience and Biobehavioral Reviews 107 (2019) 399–421

on growth charts. When multiple groups of diet manipulation lengths have been used: + = separate experimental groups; When multiple tests have been used: ^ = ongoing test without training between test sessions; # =
Experimental details and behavioural outcomes for studies examining the effect of dietary manipulation on hippocampal-dependent learning and memory in the spontaneous alternation task. (*Approximate age based
Wu et al., 2003). Mixed results were reported in one study using mice,

Rats consuming the western diet had a significantly lower

Mice consuming the HFD t showed significantly reduced

There was no effect of diet on percentage of sequential

There was no effect of diet on percentage of sequential

There was no effect of diet on percentage of sequential

in which a deficit was detected on a place recognition task after a 24 -

Mice consuming the HFD showed significantly reduced

Mice consuming the HFD showed significantly reduced

percentage of sequential arm entries than control rats.
hour retention period but not a 1 -hour retention period (Valladolid-

spontaneous alternation than mice consuming CD.

spontaneous alternation than rats consuming CD.

spontaneous alternation than rats consuming CD.

Acebes et al., 2013, Experiment 3). Mixed results were also reported in
four experiments using rats: one study reported a deficit on time in
target quadrant on the Morris water maze in rats consuming HFD but
not HSD (Gergerlioglu et al., 2016); one reported a deficit on the Y-
maze after 10 days of a high fat-high sugar diet, but no deficit after 40
days of the diet, nor after 10 or 40 days of a high fat diet (Hargrave
et al., 2016); one reported a deficit measuring time spent in target
Behavioural Outcomes

quadrant on the Morris water maze task at a 10 day retention interval

but not a 24-hour retention interval (Jurdak et al., 2008), and one re-
ported impaired learning in the Morris water maze task but no differ-
arm entries.

arm entries.

arm entries.
ence in the time spent in the target quadrant at test (Kendig et al.,
2013). Thus, diet-induced impairments on hippocampal-dependent
spatial learning and memory do not appear to be specific to rodent
species.
Behavioural Task (Dependent Variable)

(percentage sequential arm entries)

4.3. Sex as a variable for diet-induced cognitive impairment

Y-Maze Spontaneous Alternation
T-Maze Spontaneous Alternation

T-Maze Spontaneous Alternation

Y-maze Spontaneous Alternation

Sex differences in hippocampal-dependent spatial learning and

memory are well documented in both humans and rodents (reviewed in
Keeley et al., 2015; Koss and Frick, 2017; Yagi and Galea, 2018), with
isolated test involving training and testing. CD = control diet; HFD = high fat diet; HFHS = high fat-high sugar diet; HSD = high sugar diet).

the bulk of the evidence suggesting a male advantage in spatial navi-

gation (Astur et al., 2016; Moffat et al., 1998; Piber et al., 2018), and a
female advantage in place recognition (Voyer et al., 2007, 2017). Such
differences have been suggested to be due sex hormones (reviewed in
Brake and Lacasse, 2018; Ervin and Choleris, 2019; Hammes and Levin,
2019), such as the differential role of estradiol on hippocampal synaptic
Diet duration Before

plasticity in males and females (Bäumler et al., 2019; Jain et al., 2019;
Wang et al., 2018). Males have typically been used to examine dietary
effects on hippocampal-dependent tasks. When females have been in-
Behaviour

40 days+

10 days+

40 days+

cluded, the experimental designs often lack direct comparison between

8 weeks

8 weeks
17 days

10 days

the sexes (e.g. use of female subjects only, or collapsing across male and
female data points for analysis). Of the 41 articles included in the
present meta-analysis, five articles used female subjects across six ex-
Age* at Diet Onset

periments (Abbott et al., 2016; Jamshed et al., 2014; Kendig et al.,

7+ weeks* (275-

10 months old

2013; Molteni et al., 2004; Pratchayasakul et al., 2015), with deficits

observed in object location memory (Abbott et al., 2016) and in
300 grams)
8 weeks

8 weeks

learning (Kendig et al., 2013) and remembering the platform location

(Jamshed et al., 2014; Molteni et al., 2004) in the Morris water maze
task. Two of these studies collapsed male and female data for analysis
HFHS (labelled H igh-fat, high-dextrose

(Jamshed et al., 2014; Kendig et al., 2013), and another two studies
used only female subjects (Molteni et al., 2004; Pratchayasakul et al.,
2015). Of the included studies, only Abbott et al. (2016) specifically
compared the influence of a high-sugar diet on the performance of male
“Western” Diet by authors)

and female rats in place recognition and object-in-place memory tasks.

They reported that both males and females were impaired in the place
Experimental Diet

recognition task, and males but not females were impaired on object-in-
Ketogenic Diet
Moderate HFD
Extreme HFD

place memory, perhaps indicating that female rats have better memory
for object-in-place configurations than male rats (e.g. Cost et al., 2012).
HFD

4.4. Age as a variable for diet-induced cognitive impairment

ICR mice [Male]
Species & Strain

Sprague Dawley
C57BL/6 J mice

Adolescents may be more susceptible than adults to the effects of

dietary manipulations on hippocampal-dependent learning and
rats [Male]

memory (reviewed in Noble and Kanoski, 2016) and hippocampal

[Male]
[sex]

morphology and function in general (Del Olmo and Ruiz Gayo, 2018).
The transition from adolescence to adulthood occurs at approximately
postnatal day 63 (9 weeks) in rats (Sengupta, 2011, 2013) and postnatal
Hargrave et al (2016)

day 70 (10 weeks) in mice (Dutta and Sengupta, 2016). Using these
Arnold et al (2014)

Park et al (2018)

ages as a cut-off, we extracted 27 experiments from 24 articles that

Author & Expt

manipulated the diet during adolescence (i.e., when aged less than 9
Expt 1

weeks in rats and less than 10 weeks in mice), and nine experiments
Table 8

extracted from nine articles that provided dietary manipulations to

subjects in adulthood. The remaining eight articles combined both

414
K.N. Abbott, et al. Neuroscience and Biobehavioral Reviews 107 (2019) 399–421

Fig. 2. Forest plots and meta-analysis results of experiments using a high fat diet. (6-armWM = radial 6-arm water maze; F = female; ExtHF = extreme high fat diet;
HF = high fat diet; KetoDiet = ketogenic diet; M = male; ModHF = moderate high fat diet; MWM = Morris water maze - dependent variable when not time in
target quadrant (Distfromplat = distance from platform); SA = spontaneous alternation; wks = weeks).

adolescents and adults in their control and dietary manipulation con-
ditions (Beilharz et al., 2014, 2018; Denver et al., 2018; Hargrave et al.,
2016; Kanoski and Davidson, 2010; Kendig et al., 2013; Tran and
Westbrook, 2015, 2018). Deficits in hippocampal-dependent spatial
learning and memory was observed in 15 experiments (56%) using
adolescent animals (Abbott et al., 2016; Alzoubi et al., 2013a, 2013b,
2018; Arnold et al., 2014; Jamshed et al., 2014; Liang et al., 2015;
Mirzaei et al., 2018; Molteni et al., 2004; Pathan et al., 2008; Spinelli
et al., 2017; Valladolid-Acebes et al., 2011, 2013, Experiment 1; Xu
et al., 2018; Xu and Reichelt, 2018) and in five experiments (56%)
using adults (Che et al., 2018; Moreira et al., 2014; Park et al., 2018;
Thirumangalakudi et al., 2008). Nine experiments failed to detect im-
pairments in adolescents (Ayabe et al., 2018; Magnusson et al., 2015;
Ross et al., 2013; Scichilone et al., 2016; Silva et al., 2005; Takechi
et al., 2017; Woodie and Blythe, 2018; Wu et al., 2004) and three failed
to detect impairments in adult (Boitard et al., 2014; Pratchayasakul
et al., 2015; Spencer et al., 2017). Mixed results were reported in three
experiments using adolescents (Abbott et al., 2016; Jurdak et al., 2008;
Valladolid-Acebes et al., 2013, Experiment 3) and one experiment using
adults (Gergerlioglu et al., 2016). Thus, the findings from the articles
included in the present analysis suggests that the use of adolescent or
adult subjects is not a critical factor in determining the impact of
dietary manipulations on hippocampal-dependent spatial learning and
memory. Nevertheless, future meta-analyses may wish to consider age
at the start of the dietary manipulation as a moderator of diet-induced
hippocampal impairment.
4.5. Body weight, metabolic changes, and diet-induced cognitive
impairments
Our meta-analyses focused on the composition of the diet and the
task used to assess the effects of the diet on cognition. However, we now
consider the evidence from the included studies regarding the effects of
the diet on body weight and metabolic changes (see Table 1). Of the 32
experiments using a HFD: nine experiments did not provide information
regarding body weight, 18 reported a significant difference in body
weight between control and experimental animals at the time of be-
havioral testing (Alzoubi et al., 2013a, 2013b; Arnold et al., 2014;
Ayabe et al., 2018; Boitard et al., 2014; Denver et al., 2018; Jurdak
et al., 2008; Magnusson et al., 2015; Park et al., 2018; Pathan et al.,
2008; Spencer et al., 2017; Valladolid-Acebes et al., 2011, 2013; Wei
et al., 2018; Woodie and Blythe, 2018; Xu et al., 2018); four reported no
significant difference in body weight (Gergerlioglu et al., 2016;
Magnusson et al., 2015; Moreira et al., 2014; Scichilone et al., 2016);

Fig. 3. Forest plots and meta-analysis results of experiments using a high sugar diet. (F = female; HFruc = high fructose diet; HS = high sugar diet; M = male;
MWM = Morris water maze - dependent variable when not time in target quadrant (Distfromplat = distance from platform); wks = weeks).

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K.N. Abbott, et al. Neuroscience and Biobehavioral Reviews 107 (2019) 399–421

Fig. 4. Forest plots and meta-analysis results of experiments using a high fat-high sugar diet. (F = female; HFHFruc = high fat high fructose diet; HFHS = high fat-
high sugar diet; M = male; MWM = Morris water maze; SA = spontaneous alternation; wks = weeks).

Fig. 5. Forest plots and meta-analysis results of experiments using a Morris water maze (MWM). All studies used time in target quadrant as the depdent variable,
unless otherwise stated. (Distfromplat = distance from platform; F = female; HF =high fat diet; HFruc = high fructose diet; HFHFruc = high fat-high fructose diet;
HFHS = high fat-high sugar diet; HS = high sugar diet; M = male; wks = weeks).

Fig. 6. Forest plots and meta-analysis results of experiments using a place recognition task. (F = female; HF = high fat diet; HFHS = high fat-high sufar diet; HS =
high sugar diet; M = male; wks = weeks).

and one reported a significant difference in body weight for rats con-
suming the diet from 8 weeks of age, but not for rats consuming the diet
from 4 weeks (Pratchayasakul et al., 2015). Of the experiments re-
porting a significant difference in body weight between control and
experimental animals: three reported a deficit on the RAM or RAWM
(Alzoubi et al., 2013a, 2013b; Valladolid-Acebes et al., 2011); three
reported a deficit on the MWM (Pathan et al., 2008; Wei et al., 2018; Xu
et al., 2018); two reported a deficit on the reversal stage of the MWM
despite intact performance during the probe test for the original plat-
form location (Magnusson et al., 2015; Woodie and Blythe, 2018); three
reported deficits in spontaneous alternation (Arnold et al., 2014, Ex-
treme HFD & Moderate HFD; Park et al., 2018); and one reported a
deficit in place recognition (Valladolid-Acebes et al., 2013, Experiment
1). The remaining experiments that reported body weight differences
failed to detect an effect of diet manipulation on the MWM (Boitard
et al., 2014; Denver et al., 2018; Jurdak et al., 2008; Magnusson et al.,

416
K.N. Abbott, et al.
Fig. 7. Forest plots and meta-analysis results of experiments using a radial arm or radial arm water maze (WM). (HF = high fat diet; HFHS = high fat-high sugar diet;
M = male; wks = weeks).
Fig. 8. Forest plots and meta-analysis results of experiments using a spontaneous alternation (SA) task. (HF = high fat diet; HFHS = high fat-high sugar diet; M =
male; wks = weeks).
2015; Pratchayasakul et al., 2015; Spencer et al., 2017; Woodie and
Blythe, 2018), in place recognition (Ayabe et al., 2018; Valladolid-
Acebes et al., 2013, Experiment 3), or in spontaneous alternation
(Hargrave et al., 2016). Of the studies reporting no significant differ-
ence in body weight: one reported a deficit on the MWM (Gergerlioglu
et al., 2016) and one reported a deficit in Place recognition (Moreira
et al., 2014); the remaining two studies reported no behavioural deficit
on the MWM (Scichilone et al., 2016) or in place recognition
(Magnusson et al., 2015).
Of the nine experiments using a HSD, only one experiment (Jurdak
et al., 2008) reported a significant difference in body weight between
control and experimental animals at the time of behavioural testing and
a dietary-induced deficit in MWM. The remaining eight experiments
reported no significant difference in body weight (Abbott et al., 2016;
Beilharz et al., 2014; Gergerlioglu et al., 2016; Magnusson et al., 2015).
Of these reporting no difference in body weight: four experiments re-
ported a deficit in place recognition (Abbott et al., 2016; Beilharz et al.,
2014; Xu and Reichelt, 2018); one reported a deficit in the MWM
(Kendig et al., 2013). The remaining experiments reported no deficit in
place recognition (Magnusson et al., 2015) or the MWM (Gergerlioglu
et al., 2016; Magnusson et al., 2015).
Of the 11 studies using a HFSD, four reported a significant differ-
ence in body weight between control and experimental animals at the
time of behavioral testing (Beilharz et al., 2018; Kanoski and Davidson,
2010; Ross et al., 2013; Takechi et al., 2017); one reported no sig-
nificant difference in body weight (Woodie and Blythe, 2018); one re-
ported a significant difference in total body fat but not body weight
(Hargrave et al., 2016); and three reported a significant difference in
body weight at later, but not early, behavioural tests (Beilharz et al.,
2014, Experiments 1 and 2; Tran and Westbrook, 2015). Of the studies
reporting a significant difference in body fat or body weight at one or
more behavioural test point: four reported a deficit in place recognition
(Beilharz et al., 2014, Expeirments 1 and 2; Beilharz et al., 2018; Tran
and Westbrook, 2015): one reported a deficit in spontaneous alterna-
tion (Hargrave et al., 2016; HFHS 10 days); and one reported a deficit in
the RAM (Kanoski and Davidson, 2010). The remaining experiments
reported no deficits in place recognition (Ross et al., 2013),
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Neuroscience and Biobehavioral Reviews 107 (2019) 399–421
spontaneous alternation (Hargrave et al., 2016; HFHS 40 days, Keto-
genic 10 and 40 days), or the MWM (Takechi et al., 2017). Taken to-
gether, the experiments included in the present meta-analysis provide
equivocal evidence regarding the association between dietary-induced
increases in body weight and cognitive performance; increases in body
weight and cognitive deficits do co-occur but deficits have been de-
tected in the absence of increases in body weight and cognition has
been intact in spite of increases in body weight.
The studies included in the meta-analysis differed with respect to
their assessment of diet-induced alterations to metabolic status. A
number of studies demonstrating diet-induced cognitive deficits report
significant differences between control and experimental animals in
metabolic parameters including blood glucose level (Arnold et al.,
2014; Jurdak et al., 2008; Pathan et al., 2008; Xu et al., 2018), response
on a glucose tolerance test (Arnold et al., 2014; Xu et al., 2018) and
insulin tolerance test (Xu et al., 2018), plasma insulin level (Beilharz
et al., 2014, Experiment 1; Pathan et al., 2008; Spinelli et al., 2017;
Valladolid-Acebes et al., 2011), plasma leptin level (Beilharz et al.,
2014, Experiment 2; Valladolid-Acebes et al., 2013, Experiment 1),
triglycerides (Beilharz et al., 2014, Experiment 2; Jamshed et al., 2014;
Jurdak et al., 2008; Moreira et al., 2014; Pathan et al., 2008; Xu et al.,
2018), and cholesterol levels (Jamshed et al., 2014; Moreira et al.,
2014; Pathan et al., 2008; Xu et al., 2018). However, a number of the
included studies also failed to find statistically significant differences in
these metabolic parameters (Beilharz et al., 2014, 2018; Gergerlioglu
et al., 2016; Jurdak et al., 2008; Kendig et al., 2013; Moreira et al.,
2014; Valladolid-Acebes et al., 2011, 2013). Furthermore, dietary-in-
duced alterations in blood glucose (Boitard et al., 2014; Kendig et al.,
2013; Scichilone et al., 2016; Takechi et al., 2017; Valladolid-Acebes
et al., 2013, Experiment 3), plasma insulin and HOMA (Pratchayasakul
et al., 2015; Takechi et al., 2017), and plasma leptin (Boitard et al.,
2014; Valladolid-Acebes et al., 2013, Experiment 3) have been reported
but in the absence of deficits in hippocampal-dependent learning and
memory. Thus, again, the experiments included in the meta-analysis
provide equivocal evidence regarding the association between meta-
bolic changes and cognitive performance.
K.N. Abbott, et al.
4.6. Mechanisms of diet-induced impairments
There are various mechanisms by which high fat, high sugar, or high
fat-high sugar diets can impair hippocampal-dependent forms of cog-
nition (reviewed in Beilharz et al., 2015; Freeman et al., 2014). One
such mechanism is neuroinflammation (Guillemot-Legris, and Muccioli,
2017). Several studies have reported that diet-induced impairments are
accompanied by increased expression of pro-inflammatory cytokines,
such as interleukin-1β (IL-1β; Beilharz et al., 2014, 2018; Che et al.,
2018; Mirzaei et al., 2018; Thirumangalakudi et al., 2008), tumor ne-
crosis factor-α (TNF-α) mRNA (Beilharz et al., 2014; Thirumangalakudi
et al., 2008) and protein (Che et al., 2018), as well as glial fibrillary
acidic protein (GFAP), a marker of glial cell activation, (Che et al.,
2018; Thirumangalakudi et al., 2008). However, inconsistent results
have been reported in rodents who failed to exhibit diet-induced im-
pairments: some studies failed to detect evidence for pro-inflammatory
cytokine expression (Boitard et al., 2014; Takechi et al., 2017) and
GFAP (Denver et al., 2018; Silva et al., 2005), whereas others found
increased expression of IL-1β and TNF- α protein (Ayabe et al., 2018;
Spencer et al., 2017). Thus, the presence of neuroinflammation is not a
necessarily condition for observing short-term dietary impairments in
hippocampal-dependent spatial learning and memory.
A second mechanism is reductions in neuroplasticity (Morin et al.,
2017; Murphy et al., 2014). Several studies have reported that diet-
induced impairments are associated with reduced long-term potentia-
tion in hippocampal pyramidal neurons (Spinelli et al., 2017) and
changes in factors related to neuroplasticity, such as decreases in sy-
napsin-1 mRNA and protein (Molteni et al., 2004), as well as in Brain
Derived Neurotrophic Factor (BDNF) mRNA and protein (Che et al.,
2018; Molteni et al., 2004). Consistent with a role for changes in neu-
roplasticity, some studies failed to detect any changes in BDNF mRNA
(Wu et al., 2003) or BDNF protein expression (Woodie and Blythe,
2018; Wu et al., 2003) in rodents who failed to exhibit diet-induced
impairments in spatial learning and memory. However, other studies
have reported diet-induced impairments, but in the absence of changes
to BDNF mRNA (Alzoubi et al., 2013a, 2013b) or BDNF protein ex-
pression (Beilharz et al., 2014). Conversely, markers of altered neuro-
plasticity, such as increased synaptophysin protein (Denver et al.,
2018), decreased dendritic spine density, as well as both increases
(Ayabe et al., 2018) and decreases (Scichilone et al., 2016) in BDNF
protein expression, have been found in rodents who failed to exhibit
diet-induced impairments in spatial learning and memory. Taken to-
gether, changes in neuroplasticity may play a role in mediating the
cognitive impairments induced by relatively short-term dietary ex-
posures but the nature of this role remains to be determined.
Finally, additional mechanisms include altered insulin signaling
within the hippocampus (Arnold et al., 2014; Liang et al., 2015; Spinelli
et al., 2017; Xu et al., 2018), disruptions to the blood-brain-barrier (Hsu
and Kanoski, 2014), and dysbiosis in the gut microbiome arising from
reduced bacterial diversity (Beilharz et al., 2018; Magnusson et al.,
2015; Noble et al., 2017). However, these proposals are relatively re-
cent and they await further investigation (Denver et al., 2018;
Pratchayasakul et al., 2015).
5. Conclusion
In sum, the meta-analysis showed that, despite the inconsistent
findings in the literature, diets high in saturated fat or refined sugar can
each produce reliable impairments in hippocampal-dependent forms of
cognition. It also showed that these impairments can be detected in a
range of hippocampal-dependent tasks. These results reveal that the
type of dietary manipulation is unlikely to be the primary factor for the
inconsistent findings in the literature. Instead, we propose that the in-
consistencies are more likely to be a product of the procedural varia-
tions used to assess the impact of short-term diet exposures on cogni-
tion. Finally, while no direct statistical comparisons were made in this
418
Neuroscience and Biobehavioral Reviews 107 (2019) 399–421
type of meta-analysis conducted, the weighted effect-sizes suggest that
diet-induced impairments are most likely to be detected in rodents fed a
high fat-high sugar diet and tested in the radial arm maze.
Acknowledgement
Kirsten Abbott was supported by an Australian Government
Research Training Program Scholarship.
Appendix A
Search Terms and Strategy
A search was conducted on PubMed for the following terms:
High Fat Diet:
(((((((((high fat[Title/Abstract]) AND memory[Title/Abstract]) OR
fat[Title/Abstract]) AND diet[Title/Abstract]) AND memory[Title/
Abstract]) OR high fat[Title/Abstract]) AND cognit*[Title/Abstract])
OR fat[Title/Abstract]) AND diet[Title/Abstract]) AND cognit*[Title/
Abstract]
High Sugar Diet:
((((((((high sugar[Title/Abstract]) AND memory[Title/Abstract])
OR sugar[Title/Abstract]) AND diet[Title/Abstract]) AND memory
[Title/Abstract]) OR high sugar[Title/Abstract]) AND cognit*[Title/
Abstract]) OR sugar[Title/Abstract]) AND cognit*[Title/Abstract]
High Fat Sugar Diet:
(((((((Western diet) AND memory) OR cafeteria diet[Title/
Abstract]) AND memory[Title/Abstract]) OR Western diet[Title/
Abstract]) AND cognit*[Title/Abstract]) OR cafeteria diet[Title/
Abstract]) AND cognit*[Title/Abstract]
A search on Proquest was conducted using the search terms:
High Fat Diet:
ab(high fat) AND ab(memory) OR ab(fat) AND ab(diet) AND ab
(memory) OR ab(high fat) AND ab(cognit*) OR ab(fat) AND ab(diet)
AND ab(cognit*)
High Sugar Diet:
ab(high sugar) AND ab(memory) OR ab(sugar) AND ab(diet) AND
ab(memory) OR ab(high sugar) AND ab(cognit*) OR ab(sugar) AND ab
(diet) AND ab(cognit*)
High Fat Sugar Diet:
ab(western diet) AND ab(memory) OR ab(cafeteria diet) AND ab
(memory) OR ab(Western diet) AND ab(cognit*) OR ab(cafeteria diet)
AND ab(cognit*)
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